Project Summary: During the past decade, it has become clear that the rate at which crossing over occurs across the genome has a substantial influence on the impact of natural selection on molecular variation. Recent studies are confirming theoretical predictions that adaptively evolving genes are most often found in regions of chromosomes where crossing over is most frequent. One large gap in our knowledge is the relationship of population structure to forces such as natural selection and genetic drift that are mediated by variation in rates of recombination across the genome. Because many eukaryotic, outcrossing organisms exist in structured populations at present or some time during their ancestry, knowledge about the effects of population subdivision and migration are critical to understanding of the evolutionary mechanisms shaping the levels and patterns of variation in genomes. We estimate the interplay between natural selection, population subdivision, genetic drift, and crossing over rates in Drosophila ananassae, a species that exists in highly structured populations in nature, with a known biogeography, and for which the genome has been sequenced and will soon be annotated. Extensive genetic and physical maps are already available. We will densely map the entire genome using molecular markers both genetically and physically to estimate rates of recombination across the three major chromosomes. We will further identify adaptively evolving genes and estimate the impact of population structure, natural selection, and genetic drift in the context of variation in recombination rates at a fine scale. We will make use of scaffolds from the D. ananassae genome sequence and high throughput genotyping technology as well as cutting-edge statistical approaches to explore various hypotheses that make predictions about the influence of population structure and recombination on adaptive evolution. Finally, we will estimate the frequency of inversion polymorphisms across the three major chromosomes that may have an influence on evolutionary forces that determine the levels and patterns of variation across the chromosomes. Graduate and undergraduate training are integrated into the experimental approaches in this AREA proposal, and thus student training is a major objective. [unreadable] [unreadable] RELEVANCE: The studies we propose will be the first comprehensive investigation of how rates of recombination mediate the effects of adaptive evolution in subdivided populations. They will extend our understanding of how natural selection, genetic drift and crossing over impact molecular variation to include the effects of migration on genome variation, a common feature of the ancestral history of many outcrossing eukaryotic organisms. Such knowledge is critical for understanding the mechanisms determining the distribution of genetic traits in natural populations, including human genetic diseases. [unreadable] [unreadable] [unreadable]